Comprehensive genetic analysis of ALS-related genes in Japanese sporadic ALS patients

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19485
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: NAKAMURA Ryoichi 名古屋大学, 医学部附属病院, 医員 (80723030)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 筋萎縮性側索硬化症 / ALS / 次世代シークエンサー / 網羅的遺伝子解析 / 遺伝子変異 / 分子疫学

Outline of Final Research Achievements

To investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients, we designed a multiplex, PCR-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from Japanese sporadic ALS patients using an Ion Torrent PGM sequencer. We identified the known ALS pathogenic variants and predicted the functional properties of novel non-synonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored one or two novel non-synonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients.

Free Research Field

神経内科学